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Circulating MicroRNAs as Novel Biomarkers for Platelet Activation.
MedLine Citation:
PMID:  23283721     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rationale: MicroRNA biomarkers are attracting considerable interest. Effects of medication, however, have not been investigated thus far. Objective: To analyse changes in plasma microRNAs in response to anti-platelet therapy. Methods and Results: Profiling for 377 microRNAs was performed in platelets, platelet microparticles, platelet-rich plasma, platelet-poor plasma and serum. Platelet-rich plasma showed markedly higher levels of microRNAs than serum and platelet-poor plasma. Few abundant platelet microRNAs, such as miR-24, miR-197, miR-191, and miR-223, were also increased in serum compared to platelet-poor plasma. In contrast, anti-platelet therapy significantly reduced microRNA levels. Using custom-made qPCR plates, 92 microRNAs were assessed in a dose-escalation study in healthy volunteers at four different time points: at baseline without therapy, at 1 week with 10mg prasugrel, at 2 weeks with 10mg prasugrel+75mg aspirin and at 3 weeks with 10mg prasugrel+300mg aspirin. Findings in healthy volunteers were confirmed by individual TaqMan qPCR assays (n=9). Validation was performed in an independent cohort of patients with symptomatic atherosclerosis (n=33) who received low dose aspirin at baseline. Plasma levels of platelet microRNAs, such as miR-223, miR-191 and others, i.e. miR-126 and miR-150, decreased upon further platelet inhibition. Conclusions: Our study demonstrated a substantial platelet contribution to the circulating microRNA pool and identified microRNAs responsive to anti-platelet therapy. It also highlights that anti-platelet therapy and preparation of blood samples could be confounding factors in case-control studies relating plasma microRNAs to cardiovascular disease.
Authors:
Peter Willeit; Anna Zampetaki; Katarzyna Dudek; Dorothee Kaudewitz; A S King; Nicholas S Kirkby; Roxanne Crosby-Nwaobi; Marianna Prokopi; Ignat Drozdov; Sarah Langley; Sobha Sivaprasad; Hugh S Markus; Jane A Mitchell; Tim Warner; Stefan Kiechl; Manuel Mayr
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Department of Public Health and Primary Care, University of Cambridge, Darwin College, Silver Street, Cambridge, CB39EU, UNITED KINGDOM.
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